305 51Cr-EDTA-measured intestinal permeability and serum levels of acute-phase reactants and111 Inlabeled leukocyte scans.32 In UC, a significant correlation between 51Cr-EDTA-measured intestinal permeability and endoscopic disease activity was demonstrated.26 In CD, it has been shown that anti-TNF treatment attenuates mucosal inflammation and also improves intestinal integrity measured by orally administered 51Cr-EDTA.54 Although the relationship between disease activity and Cr-EDTA-measured intestinal permeability seems to be well-established, studies show weak comparability because of various study designs, different intestinal permeability tracers and varying time intervals. Furthermore, it is difficult to clearly demonstrate this relationship since many factors are known to affect intestinal permeability, such as disease localization, surgical history, alcohol consumption, medication use, commensal bacteria and many dietary components.55 As a consequence, the extent of this relationship remains inconclusive. In addition, all the previously mentioned studies are remarkably contradictory as to the primary intestinal location and degree of increased 51Cr-EDTA bowel passage.25-29 In our study cohort, CD patients with exclusively colonic disease activity showed a higher median urinary 52Cr-EDTA/creatinine excretion as compared to patients with ileal involvement, though non-significantly. Similarly, we could not demonstrate any statistically significant differences in intestinal permeability between three different subgroups of disease localization (i.e. ileal, colonic or ileocolonic disease). Until now, it remains unclear whether increased intestinal permeability is secondary to subclinical mucosal inflammation in CD or vice versa.56,57 Accumulating evidence suggests that increased intestinal permeability may be the consequence of a genetically pre-existing epithelial barrier abnormality in certain individuals that predisposes them to the onset of intestinal inflammation.58 Various studies have shown that a subset of clinically healthy first-degree relatives of Crohn’s disease patients show increased intestinal permeability as compared to healthy controls.15,16 Moreover, it has been hypothesized that impaired intestinal permeability may already be apparent long before any mucosal inflammation is present and could be predictive of clinical relapse. In addition, another study demonstrated that in first-degree relatives of CD patients subclinical intestinal inflammation is present, reflected by an increased fecal calprotectin level.59 In our study, we found a significant correlation between intestinal inflammatory disease activity (as represented by fecal calprotectin levels) and intestinal permeability (as measured by urinary 52Cr EDTA excretion). Overall, this indicates that 52Cr-EDTA-measured intestinal permeability might be particularly useful in defining the first stages of development of Crohn’s disease in a subgroup of unaffected, genetically susceptible individuals. CD patients typically demonstrate a decreased gut microbiota diversity as compared to healthy individuals.60 An important observation in CD is the reduction in the commensal anaerobic, butyrate-producing bacterium F. prausnitzii, as well as an increased number of Enterobacteriaceae (e.g. Escherichia coli).3,6,61 In the present study, we observed a negative nonsignificant relationship between 52Cr-EDTA-measured intestinal permeability and the relative abundance of F. prausnitzii, while a positive non-significant relationship was observed between the relative abundance of Enterobacteriaceae and urinary 52Cr-EDTA excretion in CD patients. These interesting associations (though moderate and non-significant) support the existence of a link between the gut microbiota composition and the integrity of the intestinal barrier. Future 52Cr-EDTA intestinal permeability in Crohn’s disease
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